Behavioral assays have been developed to proceed with an integrated, selective molecular genetic analysis of learning and memory processes in Drosophila. Initial results have revealed substantial functional homology between fruit flies and vertebrates for these behavioral properties of learning and memory (see Preliminary Results). A better understanding of the functional relations between molecular processes and learning/memory processes will emerge by determining more precisely which properties are disrupted by particular single-gene mutations. Assays for discriminative Pavlovian conditioning, acquisition, extinction, US pre- exposure, blocking and overshadowing, conditioned inhibition, conditioned excitation, retrograde amnesia, long-term memory, trace conditioning and habituation, dishabituation and spontaneous recovery already have been developed, and results from wild-type (normal) flies are presented. Ne assays for CS-pre-exposure, CS preconditioning, second-order conditioning, short-term memory, middle-term memory and sensitization also will be developed. The learning/memory mutants dunce rutabaga, radish, amnesiac, latheo, linotte, nalyot and golovan, the ion channel mutants Shaker, ether-a-gogo and no action potential, the brain-structure mutants mushrooms body degraded, mushroom body miniature, calyx, bulging, minibrain, central body defect, no bridge and central complex broad and biochemical mutants of the RI regulatory subunit of cAMP-dependent protein kinase (PKA) and the catalytic subunit of PKA will be characterized with this battery of behavioral assays. This experimental approach promises a genic dissection of the functional relations between molecular processes and learning/memory processes and of the functional relations among the various behavioral properties themselves. Considering the substantial molecular homologies among fruit fly, other invertebrate and vertebrate learning and memory processes, we expect the knowledge derived from our work with fruit flies to suggest a biological organization of vertebrate cognition. Importantly, this experimental approach is unique to the field of cognitive neuropsychology.